Endocrinology, Diabetes and Metabolism最新文献

Introduction

ANGPTLs (Angiopoietin-like proteins) 3 and 4 play an important role in the development of type 2 diabetes. These glycoproteins affect the modulation of glucose and lipid metabolism. They inhibit lipoprotein lipase (LPL) activity and provoke lipolysis. This study was aimed to investigate the protein levels of ANGPTL3 and 4 in the serum of type 2 diabetic patients with metabolic syndrome in comparison to the type 2 diabetic patients without metabolic syndrome and the control group.

Methods

Three groups of individuals were included in this study; Group I: 47 patients with type 2 diabetes and metabolic syndrome; Group II: 25 patients with type 2 diabetes without metabolic syndrome; Group III: 40 non-diabetic healthy people without metabolic syndrome as a control group. After collection of 5 mL fasting blood samples, serum concentrations of fasting blood sugar (FBS), cholesterol (Chol), triglyceride (TG), HDL-C (High-density lipoprotein-Cholesterol) and LDL-C (Low-density lipoprotein-Cholesterol) were measured by the enzymatic method; blood pressure (BP), height and weight with stadiometers; and ANGPTL3 and 4 by the enzyme-linked immunosorbent assay (ELISA).

Results

The serum levels of ANGPTL3 was significantly different among our three groups (p = .000). In patients with type 2 diabetes and metabolic syndrome (Group I), ANGPTL3 and 4 levels were lower than the control group.

The serum levels of the parameters evaluated in this study (except HDL-C) was lower in the group II in comparison with the group I, and this difference was significant for TG, Chol, BP and BMI between these two groups. Also, our results revealed that there was a negative correlation between FBS, TG, Chol, LDL-C and BMI with ANGPTL3 and 4. While, there was a significant positive correlation between ANGPTL4 and ANGPTL3.

Conclusion

Altogether, our findings suggest that the decreased levels of ANGPTL3 and 4 may be a causative factor for type 2 diabetes.

Objective

The objective of this systematic literature review (SLR) was to summarize the latest studies evaluating the burden of illness in endogenous Cushing's syndrome (CS), including the impact of CS on overall and domain-specific health-related quality of life (HRQoL) and the economic burden of CS to provide a holistic understanding of disease and treatment burden.

Methods

An SLR was conducted in PubMed, MEDLINE and Embase using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to identify peer-reviewed manuscripts and conference abstracts published in English from 2015 to December 4, 2020.

Results

Forty-five publications were eligible for inclusion; data were extracted from 37 primary studies while 8 SLRs were included for reference only. Thirty-one studies reported HRQoL using validated patient reported outcome (PRO) measures in pre- or post-surgery, radiotherapy and pharmacotherapy patients. Overall, this SLR found that patients with CS have worse outcomes relative to healthy populations across specific dimensions, such as depression, despite an improvement in HRQoL post-treatment. These findings reveal that CS symptoms are not fully resolved by the existing care paradigm. Few studies report on the economic burden of CS and currently available data indicate a high direct healthcare system cost burden.

Conclusions

Patients with CS experience a significant, complex and multifactorial HRQoL burden. Symptom-specific burden studies are sparse in the literature and the understanding of long-term CS symptomatic burden and economic burden is limited. This review intends to provide an updated reference for clinicians, payers and other stakeholders on the burden of CS as reported in published literature and to encourage further research in this area.

Background

Metformin (Met) and dexamethasone (Dexa) are known to reduce blood sugar levels and anti-inflammatory effects, respectively. Based on the acceleration of atherosclerosis process in diabetes, the β-arrestin 2 (BARR2) gene and protein expression levels were evaluated in vascular smooth muscle cells (VSMCs) treated with Met and Dexa in high glucose conditions in this study.

Methods and Materials

Human VSMCs were cultured in Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM-F12) medium and, were treated with different values of Met (1 mM, 5 mM and 7 mM) and Dexa (10⁻⁷ M, 10⁻⁶ M and 10⁻⁵ M) in 24- and 48-h periods. The BARR2 gene and protein expression levels were identified with RT-qPCR and western blotting techniques, respectively. The signalling axes were predicted from gene network made using Cytoscape software and, were annotated with Gene Ontology.

Results

The BARR2 gene and protein expression levels reduced in VSMCs treated with Dexa and Met after 24- and 48-h periods. These results were more changed after 48 h. Furthermore, many BARR2-related signalling axes were found from the network genes.

Conclusion

Met and Dexa suppressed the BARR2 protein and gene expression levels in the VSMCs. Moreover, the gene network suggested some the cellular signalling axes related to BARR2 that may be affected by Met and Dexa.

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic options for addressing Type-2 diabetes, obesity, and related conditions. Among these, semaglutide, tirzepatide, liraglutide etc., all notable GLP-1RA, have gained attention owing to their favourable pharmacological properties and clinical efficacy.

Aims

This comprehensive review aims to provide a detailed analysis of both the currently available GLP-1RAs in the market and those undergoing clinical trials. The focus is on examining their mechanism of action, pharmacokinetics, efficacy in glycemic control and weight management, safety profile, and potential applications.

Materials & Methods

The review employs a systematic approach to gather information on GLP-1RAs. Relevant literature from the currently literature and ongoing clinical trials is thoroughly examined. Detailed scrutiny is applied to understand the mechanism of action, pharmacokinetic properties, and clinical outcomes of these agents.

Results

The review presents a comprehensive overview of the GLP-1RAs, highlighting their distinct mechanisms of action, pharmacokinetic profiles, and clinical effectiveness in glycemic control and weight management. Safety profiles are also discussed, providing a holistic understanding of these therapeutic agents.

Discussion

The findings are discussed in the context of advancements in the field of GLP-1RAs. Potential applications beyond diabetes and obesity are explored, shedding light on the broader implications of these agents in managing related conditions.

Conclusion

In conclusion, this review underscores the significance of GLP-1RAs, with a specific focus on semaglutide, in the management of type 2 diabetes, obesity, and beyond. By synthesizing information on their mechanisms, pharmacokinetics, efficacy, and safety, this review provides valuable insights into the potential benefits these agents offer, contributing to the ongoing discourse in the field.

Background

Identifying people with diabetes who are likely to experience a foot ulcer is an important part of preventative care. Many cohort studies report predictive models for foot ulcerations and for people with diabetes, but reports of long-term outcomes are scarce.

Aim

We aimed to develop a predictive model for foot ulceration in diabetes using a range of potential risk factors with a follow-up of 10 years after recruitment. A new foot ulceration was the outcome of interest and death was the secondary outcome of interest.

Design

A 10-year follow-up cohort study.

Methods

1193 people with a diagnosis of diabetes who took part in a study in 2006–2007 were invited to participate in a 10-year follow-up. We developed a prognostic model for the incidence of incident foot ulcerations using a survival analysis, Cox proportional hazards model. We also utilised survival analysis Kaplan–Meier curves, and relevant tests, to assess the association between the predictor variables for foot ulceration and death.

Results

At 10-year follow-up, 41% of the original study population had died and more than 18% had developed a foot ulcer. The predictive factors for foot ulceration were an inability to feel a 10 g monofilament or vibration from a tuning fork, previous foot ulceration and duration of diabetes.

Conclusions

The prognostic model shows an increased risk of ulceration for those with previous history of foot ulcerations, insensitivity to a 10 g monofilament, a tuning fork and duration of diabetes. The incidence of foot ulceration at 10-year follow-up was 18%; however, the risk of death for this community-based population was far greater than the risk of foot ulceration.

Aims

How the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D.

Materials and Methods

We post-hoc analysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24 weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time-treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses.

Results

GGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (p = .365, time-treatment interaction) and GGT (p = .510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (p < .001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW.

Conclusions

Reductions in GGT and ALT were associated with the anti-hyperglycaemic and anti-obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D.

Background

Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome of the liver, and its incidence is increasing worldwide. Accumulating evidence suggests that bile acids are associated with NAFLD. Although many studies on bile acids and NAFLD have been published over the past 20 years, the authors of this study have not found a relevant bibliometric analysis in this field. Therefore, this study aimed to evaluate the trend of publications, summarize current research hotspots and predict future research directions through bibliometric analysis in this field.

Method

Articles related to bile acids and NAFLD published between 2002 and 2022 were obtained from the Science Citation Index-Expanded of Web of Science Core Collection. Microsoft Excel, CiteSpace, VOSviewer and Bibliometric Online Analysis Platform were used to analyse the publication trends and research hotspots in this field.

Results

Among the articles published between 2002 and 2022, we retrieved 1284 articles related to bile acids and NAFLD, and finally included 568 articles. The USA was dominant until 2020, after which China surpassed the USA to become the dominant force. These two countries cooperate the most closely, and are also the most active in international cooperation. The University of California (UCL) was the most published institution, with a total of 31 publications. There were six authors who have published nine articles and ranked first. The keywords cluster labels show the 10 main clusters: #0fatty liver, #1obeticholic acid, #2oxidative stress, #37 alpha hydroxy 4 cholesten 3 one, #4deoxycholic acid, #5nonalcoholic fatty liver disease, #6mouse model, #7fibroblast growth factor 21, #8animal models, #9high-fat diet. Keywords burst analysis revealed a higher intensity of study for the nuclear receptor, FXR, and metabolic syndrome.

Conclusion

Bile acids have become an important research direction in the field of NAFLD, and the intervention of gut microbiota in NAFLD by acting on bile acids may become a potential hotspot for future research. This study provides reference and guidance for future research, and will help scholars better explore the field and innovatively discover the mechanisms and treatments of NAFLD.

Background

Despite the confirmed association between higher BMI with increased risk of the acute respiratory distress syndrome (ARDS), the association between obesity with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) is not clear. The present study aimed to investigate the association between obesity with treatment duration, ICU length of stay, and the risk of death in critically ill patients with COVID-19.

Methods

This case–control study was performed on 223 patients with COVID-19 including 148 surviving patients as the control group and 75 eventually dead patients as the case group in Rasht, Iran. Data on demographic factors, comorbidities, anthropometric measurements, the length of hospitalization and the mortality were obtained from patients' medical records.

Results

The mortality rate was significantly associated with weight (OR = 1.04, 95% CI: 1.002–1.083, p = .04), but not with BMI after adjustments for age, gender, length of stay in ICU, chronic diseases and smoking. The results did not change after further adjustments for biochemical and pathological factors.

Conclusions

Weight was positively associated with mortality after controlling for confounding variables. Further studies should consider the patient's body composition such as fat mass to establish the relationship between obesity and COVID-19 outcomes.

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood.

Methods

We used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice.

Results

We demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal-to-adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole-treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24-7, Rikenellaceae and Mucispirillum schaedleri.

Conclusions

While hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal-to-adult transition could provide additional insight into the pathophysiology of PCOS.